Adoptive immunotherapy constitutes an attempt to manipulate the immune system and involves the administration of immunologically active cells to a subject to enhance the subject's immune response to various deleterious disease states. Cancer and other types of diseases, some of which result in immunodeficiency, have exhibited positive responses to this technique. Adoptive immunotherapy first requires the removal of large numbers of lymphocytes from the subject to be treated or another subject. These cells are then cultured in vitro in immunoenhancing agents such as interleukin-2 (IL-2) or recombinant interleukin-2 (rIL-2) to generate cells having enhanced immunological activity.
One immunologically active cell population responsible for much of the beneficial activity achieved with adoptive immunotherapy is a certain Class of lymphocytes called lymphokine activated killer (LAK) cells which are derived from a progenitor cell population known as natural killer (NK) cells, or large granular lymphocytes (LGL). Both LGL and LAK cells are capable of preferentially lysing or killing certain target cells including tumor cells or virally infected cells.
When these immunologically activated cells are administered to the patient, they act to alleviate the disease state. For example, adoptive immunotherapy has been reported effective in causing regression of a variety of cancers and tumors.
Successful adoptive immunotherapy involves administering large numbers of these cells to an afflicted patient resulting in a difficult and costly procedure. As currently practiced approximately 2.times.10.sup.10 to 2.times.10.sup.11 cells are required (assuming the cells have sufficient LAK activity) for a desired response in therapy. It is first problematic to isolate from the normal lymphocyte population the LAK progenitor (LGL) cells; and second to expand these cells to yield large volumes of LAK active lymphocytes. This is particularly true when the LAK progenitor LGL are obtained by leukopheresis from subjects who are to be treated, and who are often already lymphocyte-depleted.
There is accordingly a need for a method which effectively isolates from the normal lymphocyte population the LAK progenitor cells (LGL), and expands them to yield large numbers of LAK active lymphocytes.